2. Academic Validation
  3. SARS-CoV-2 uses metabotropic glutamate receptor subtype 2 as an internalization factor to infect cells

SARS-CoV-2 uses metabotropic glutamate receptor subtype 2 as an internalization factor to infect cells

  • Cell Discov. 2021 Dec 14;7(1):119. doi: 10.1038/s41421-021-00357-z.
Jinliang Wang  # 1,  Guan Yang  # 2,  Xinxin Wang  # 1,  Zhiyuan Wen 1,  Lei Shuai 1,  Jie Luo 1,  Chong Wang 1,  Ziruo Sun 1,  Renqiang Liu 1,  Jinying Ge 1,  Xijun He 1,  Ronghong Hua 1,  Xijun Wang 1,  Xiao Yang 2,  Weiye Chen 1,  Gongxun Zhong 1,  Zhigao Bu 3
Affiliations

Affiliations

  • 1 State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, Heilongjiang, China.
  • 2 State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Beijing Institute of Lifeomics, Beijing, China.
  • 3 State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, Heilongjiang, China. [email protected].
  • # Contributed equally.
PMID: 34903715 DOI: 10.1038/s41421-021-00357-z
Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) uses angiotensin-converting Enzyme 2 (ACE2) as a binding receptor to enter cells via clathrin-mediated endocytosis (CME). However, receptors involved in other steps of SARS-CoV-2 Infection remain largely unknown. Here, we found that metabotropic glutamate receptor subtype 2 (mGluR2) is an internalization factor for SARS-CoV-2. Our results show that mGluR2 directly interacts with the SARS-CoV-2 spike protein and that knockdown of mGluR2 decreases internalization of SARS-CoV-2 but not cell binding. Further, mGluR2 is uncovered to cooperate with ACE2 to facilitate SARS-CoV-2 internalization through CME and mGluR2 knockout in mice abolished SARS-CoV-2 Infection in the nasal turbinates and significantly reduced viral Infection in the lungs. Notably, mGluR2 is also important for SARS-CoV spike protein- and Middle East respiratory syndrome coronavirus spike protein-mediated internalization. Thus, our study identifies a novel internalization factor used by SARS-CoV-2 and opens a new door for Antiviral development against coronavirus Infection.

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